AbstractLight impacts mood and cognition of humans and other animals in ways we are only beginning to recognize. These effects are thought to depend upon a specialized retinal output signal arising from intrinsically photosensitive retinal ganglion cells (ipRGCs) that is being dedicated to a stable representation of the intensity of environmental light. Insights from animal studies now implicate a previously unknown pathway in the effects of environmental light on mood. A subset of ipRGCs transmits light-intensity information to the dorsothalamic perihabenular nucleus, which in turn, innervates the medial prefrontal cortex that plays a key role in mood regulation. While the prefrontal cortex has been implicated in depression and other mood disorders, its ability to encode the level of environmental light (luminance) has never been reported. Here, as a first step to probing for a similar retino-thalamo-frontocortical circuit in humans, we used functional magnetic resonance imaging (fMRI) to identify brain regions in which activity depended on luminance level where activity was modulated either transiently or persistently by light. Twelve brain regions altered their steady-state activity according to luminance level. Most were in the prefrontal cortex or in the classic thalamocortical visual pathway; others were found in the cerebellum, caudate, and pineal. Prefrontal cortex and pineal exhibited reduced BOLD signal in bright light, while the other centers exhibited increased BOLD signals. The light-evoked prefrontal response was affected by light history and closely resembled those of ipRGCs. Although we did not find clear correspondence between the luxotonic regions in humans and those in mice, the persistence and luxotonic nature of light-evoked responses in the human prefrontal cortex may suggest that it receives input from ipRGCs, just like in the mouse. We also found seventeen regions in which activity varied only transiently with luminance level. These regions, which are involved in visual processing, motor control, and cognition, were in the cerebral cortex, diverse subcortical structures, and cerebellum. Therefore, our results demonstrate the effects of light on diverse brain centers that contribute to motor control, cognition, emotion, and reward processing.
Synaptic Dysfunction in Depression: Potential Therapeutic Targets